Die nukleare Ordnung in der Krise: William Walkers »nukleare Aufklärung« und seine Kritiker

Wie kann die internationale Staatengemeinschaft der Bedrohung durch die Proliferation von Kernwaffen und deren Trägermitteln wirksam begegnen? Diese Frage wird seit Jahrzehnten aus unterschiedlichen Blickwinkeln lebhaft erörtert. Die Mai-Ausgabe der Zeitschrift »International Affairs« spiegelt den derzeitigen Stand der Diskussion über die politisch-normativen Fundamente und die Bedrohungen und Zerfallserscheinungen der nuklearen Ordnung in umfassender Weise wider. Im Mittelpunkt steht dabei William Walkers origineller und zugleich provozierender Aufsatz über das nukleare Nichtverbreitungsregime als »Projekt der nuklearen Aufklärung«. Eine Vielzahl namhafter europäischer und amerikanischer Autoren setzt sich kritisch mit Walker auseinander. (Autorenreferat

Das iranische Atomprogramm und der Westen: Bilanz und Ausblick der nuklearen Nichtverbreitung in europäischen Fachaufsätzen

Die Frage, ob und wie der Iran zu einem Verzicht auf ein militärisches Atomprogramm bewegt werden kann, ist für die Zukunft sowohl der internationalen Sicherheit als auch speziell des globalen Nichtverbreitungsregimes von großer Bedeutung. Am 31. August 2006 ließ Teheran das vom UN-Sicherheitsrat gestellte Ultimatum verstreichen und widersetzte sich damit der Forderung, die Entwicklung eines eigenen Brennstoffkreislaufs zumindest vorübergehend auszusetzen. Die internationale Staatengemeinschaft ist nun herausgefordert, auf die Verstöße des Iran wirksam und geschlossen zu reagieren. In den Beiträgen einschlägiger Fachzeitschriften wird unter anderem der Frage nachgegangen, welche Motive der Iran haben könnte, Nuklearwaffen zu entwickeln. Einige Autoren unterziehen die diplomatischen Bemühungen der EU-3 einer kritischen Analyse. Angesichts der Gefahr einer Erosion des Nichtverbreitungsregimes werden außerdem mögliche Handlungsoptionen der internationalen Gemeinschaft diskutiert. (Autorenreferat

Vaccination-induced changes in human B-cell repertoire and pneumococcal IgM and IgA antibody at different ages

It is well known that older people are more susceptible to morbidity and mortality from infectious diseases, particularly from pulmonary diseases such as pneumococcal pneumonia where vaccines do not provide efficient protection as in younger populations. We have previously shown that the B-cell repertoire in the old is reduced and hypothesise that this may contribute to the impaired humoral responses of the elderly. Here, we investigated the repertoire and antibody responses to winter vaccination in two age groups, aged 18–49 and 65–89. We found that the serum IgM and IgA pneumococcal responses were significantly impaired in the older group, with no difference in IgG levels. IGHM spectratype analysis seems to be the most promising in terms of its predictive ability for vaccine responses. Spectratypes showed a clear change in the repertoire at day 7 after vaccination, with a return to the baseline levels at day 28. The changes at day 7 reflected expansion of IGH sequences that have smaller, more hydrophilic, CDR3 regions, and these changes were attenuated in the older group. The older group was more likely to have spectratypes indicative of a reduced diversity at day 0 and day 28. On average, the baseline repertoire in the older group was comprised of larger CDR3 regions than in the younger group. In conclusion, IgA and IgM responses are significantly impaired in the elderly pneumococcal response and are likely key mediators of protection. Hydrophilicity and/or small size of the IGH CDR3 appear to be important in these responses

Enhancement of Speed and Accuracy Trade-Off for Sports Ball Detection in Videos—Finding Fast Moving, Small Objects in Real Time

The detection and localization of the ball in sport videos is crucial to better understand events and actions occurring in those sports. Despite recent advances in the field of object detection, the automatic detection of balls remains a challenging task due to the unsteady nature of balls in images. In this paper, we address the detection of small, fast-moving balls in sport video data and introduce a real-time ball detection approach based on the YOLOv3 object detection model. We apply specific adjustments to the network architecture and training process in order to enhance the detection accuracy and speed: We facilitate an efficient integration of motion information, avoiding a complex modification of the network architecture. Furthermore, we present a customized detection approach that is designed to primarily focus on the detection of small objects. We integrate domain-specific knowledge to adapt image pre-processing and a data augmentation strategy that takes advantage of the special features of balls in images in order to improve the generalization ability of the detection network. We demonstrate that the general trade-off between detection speed and accuracy of the YOLOv3 model can be enhanced in consideration of domain-specific prior knowledge

Automated evaluation of autoantibodies on human epithelial-2 cells as an approach to standardize cell-based immunofluorescence tests

INTRODUCTION: Analysis of autoantibodies (AAB) by indirect immunofluorescence (IIF) is a basic tool for the serological diagnosis of systemic rheumatic disorders. Automation of autoantibody IIF reading including pattern recognition may improve intra- and inter-laboratory variability and meet the demand for cost-effective assessment of large numbers of samples. Comparing automated and visual interpretation, the usefulness for routine laboratory diagnostics was investigated. METHODS: Autoantibody detection by IIF on human epithelial-2 (HEp-2) cells was conducted in a total of 1222 consecutive sera of patients with suspected systemic rheumatic diseases from a university routine laboratory (n = 924) and a private referral laboratory (n = 298). IIF results from routine diagnostics were compared with a novel automated interpretation system. RESULTS: Both diagnostic procedures showed a very good agreement in detecting AAB (kappa = 0.828) and differentiating respective immunofluorescence patterns. Only 98 (8.0%) of 1222 sera demonstrated discrepant results in the differentiation of positive from negative samples. The contingency coefficients of chi-square statistics were 0.646 for the university laboratory cohort with an agreement of 93.0% and 0.695 for the private laboratory cohort with an agreement of 90.6%, P < 0.0001, respectively. Comparing immunofluorescence patterns, 111 (15.3%) sera yielded differing results. CONCLUSIONS: Automated assessment of AAB by IIF on HEp-2 cells using an automated interpretation system is a reliable and robust method for positive/negative differentiation. Employing novel mathematical algorithms, automated interpretation provides reproducible detection of specific immunofluorescence patterns on HEp-2 cells. Automated interpretation can reduce drawbacks of IIF for AAB detection in routine diagnostics providing more reliable data for clinicians

Over-Expression of LEDGF/p75 in HEp-2 Cells Enhances Autoimmune IgG Response in Patients with Benign Prostatic Hyperplasia : A Novel Diagnostic Approach with Therapeutic Consequence?

Lens epithelium-derived growth factor splice variant of 75 kDa (LEDGF/p75) is an autoantigen over-expressed in solid tumors and acts as a stress-related transcriptional co-activator. Participation of autoimmune responses in the pathophysiology of benign prostatic hyperplasia (PBH) and a corresponding immunosuppressive therapy by TNFalpha antagonists has been recently suggested. Thus, autoAb testing could aid in the diagnosis of BPH patients profiting from such therapy. We generated CRISPR/Cas9 modified HEp-2 LEDGF knock-out (KO) and HEp-2 LEDGF/p75 over-expressing (OE) cells and examined IgG autoantibody reactivity to LEDGF/p75 in patients with prostate cancer (PCa, n = 89), bladder cancer (BCa, n = 116), benign prostatic hyperplasia (BPH, n = 103), and blood donors (BD, n = 60) by indirect immunofluorescence assay (IFA). Surprisingly, we could not detect elevated binding of autoAbs against LEDGF/p75 in cancer patients, but autoAb reactivity to LEDGF/p75 OE cells in about 50% of patients with BPH was unexpectedly significantly increased. Furthermore, a line immunoassay enabling the detection of 18 different autoAbs revealed a significantly increased occurrence of anti-dsDNA autoAbs in 34% of BPH patients in contrast to tumor patients and BD. This finding was confirmed by anti-mitochondrial (mDNA) autoAb detection with the Crithidia luciliae immunofluorescence test, which also showed a significantly higher prevalence (34%) of anti-mDNA autoAbs in BPH. In summary, our study provided further evidence for the occurrence of autoimmune responses in BPH. Furthermore, LEDGF/p75 over-expression renders HEp-2 cells more autoantigenic and an ideal target for autoAb analysis in BPH with a potential therapy consequence

Porcine E. coli: Virulence-Associated Genes, Resistance Genes and Adhesion and Probiotic Activity Tested by a New Screening Method

We established an automated screening method to characterize adhesion of Escherichia colito intestinal porcine epithelial cells (IPEC-J2) and their probiotic activity against infection by enteropathogenic E. coli (EPEC). 104 intestinal E. coli isolates from domestic pigs were tested by PCR for the occurrence of virulence-associated genes, genes coding for resistances to antimicrobial agents and metals, and for phylogenetic origin by PCR. Adhesion rates and probiotic activity were examined for correlation with the presence of these genes. Finally, data were compared with those from 93 E. coli isolates from wild boars. Isolates from domestic pigs carried a broad variety of all tested genes and showed great diversity in gene patterns. Adhesions varied with a maximum of 18.3 or 24.2 mean bacteria adherence per epithelial cell after 2 or 6 hours respectively. Most isolates from domestic pigs and wild boars showed low adherence, with no correlation between adhesion/probiotic activity and E. coli genes or gene clusters. The gene sfa/foc, encoding for a subunit of F1C fimbriae did show a positive correlative association with adherence and probiotic activity; however E. coliisolates from wild boars with the sfa/foc gene showed less adhesion and probiotic activity thanE. coli with the sfa/foc gene isolated from domestic pigs after 6 hour incubation. In conclusion, screening porcine E. coli for virulence associated genes genes, adhesion to intestinal epithelial cells, and probiotic activity revealed a single important adhesion factor, several probiotic candidates, and showed important differences between E. coli of domestic pigs and wild boars

Species-specific and pathotype-specific binding of bacteria to zymogen granule membrane glycoprotein 2 (GP2)

With interest we read the paper by Juste et al 1 proposing the amount of zymogen-granule membrane glycoprotein 2 (GP2) on the surface of intestinal bacteria as a Crohn\u27s disease (CD) marker. Indeed, a decreased GP2 level was found on microbes in patients with CD as compared to those of healthy controls. GP2 is a homologue to the urinary Tamm–Horsefall protein demonstrating an antimicrobial function by binding type 1-fimbriated uropathogenic Escherichia coli (UPEC). Likewise, GP2 seems to interact with intestinal bacteria as a specific receptor of bacterial type-1 fimbriae (FimH) on intestinal microfold cells that are partaking in immune responses against such microbes.2 GP2 is overexpressed in the inflamed intestine of patients with CD and has an immunomodulating role in innate and acquired immune responses.3 ,4Interestingly, GP2 was identified as autoantigen of pancreatic antibodies in CD.4 Altogether, these findings indicate two major GP2 sources (pancreatic/intestinal) and support a role for GP2 in the interaction between the immune system and intestinal microbiota.3 Thus, loss of tolerance to GP2 could play a role in CD\u27s pathophysiology supposed to be exacerbated by preceding intestinal infections. In general, the findings by Juste et al 1 may be explained by a lower pancreatic GP2 secretion, an impaired GP2 binding to bacteria, or by a higher prevalence of bacteria with poor or no GP2 binding in patients with CD